The complement system was originally discovered as a product of hepatocytes and immune cells secreted into circulation, mediating immune responses through the classical, lectin, and alternative pathways. However, recent findings have revealed that non-immune cells, including epithelial cells, endothelial cells, neurons, pancreatic islet cells, and fibroblasts, also express complement molecules localized to organelles such as lysosomes, endoplasmic reticulum, and mitochondria, forming an intracellular complement system independent of circulating complement. Named the "complosome," this system regulates apoptosis, metabolism, autophagy, and gene expression.

In a review published in Ageing Research Reviews, a team led by Prof. He Yonghan from the Kunming Institute of Zoology (KIZ) systematically summarized the discovery, regulatory mechanisms, and aging-related functions of the complosome. The review covers the interaction between intracellular and extracellular complement, crosstalk with NF-kB, mTOR, AMPK, and MAPK pathways, and the complosome's regulation of key hallmarks of aging.

The researchers found that during aging, complement genes in multiple tissues show age-dependent upregulation, and complosome expression and activity undergo abnormal changes. Multiple functional studies confirm that the complosome participates in the development and progression of various age-related diseases, serving as a molecular link between organismal aging and age-related pathology.

The review identifies the complosome as a potential novel intervention target for aging and age-related diseases. The authors systematically summarize current complosome-targeted aging intervention strategies and discuss technical bottlenecks, opportunities, and future research directions in the field.